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Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer
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Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer
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Journal Article
Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer
2021
Overview
Background
Inhibitors targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have prolonged survival in small groups of non-small cell lung cancer (NSCLC) patients, but biomarkers predictive of the response to the immune checkpoint inhibitors (ICIs) remain rare.
Methods
The nonnegative matrix factorization (NMF) was performed for TCGA-NSCLC tumor samples based on the LM22 immune signature to construct subgroups. Characterization of NMF subgroups involved the single sample gene set variation analysis (ssGSVA), and mutation/copy number alteration and methylation analyses. Construction of RNA interaction network was based on the identification of differentially expressed RNAs (DERs). The prognostic predictor was constructed by a LASSO-Cox regression model. Four GEO datasets were used for the validation analysis.
Results
Four immune based NMF subgroups among NSCLC patients were identified. Genetic and epigenetic analyses between subgroups revealed an important role of somatic copy number alterations in determining the immune checkpoint expression on specific immune cells. Seven hub genes were recognized in the regulatory network closely related to the immune phenotype, and a three-gene prognosis predictor was constructed.
Conclusions
Our study established an immune-based prognosis predictor, which might have the potential to select subgroups benefiting from the ICI treatment, for NSCLC patients using publicly available databases.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Biomarkers, Tumor - genetics
/ Biomedical and Life Sciences
/ Carcinoma, Non-Small-Cell Lung
/ Genomics
/ Health Promotion and Disease Prevention
/ Humans
/ Immune checkpoint inhibition
/ Immune checkpoint inhibitors
/ Immune Checkpoint Inhibitors - therapeutic use
/ Immunity
/ Kinases
/ Mutation
/ Non-small cell lung carcinoma
/ NSCLC
/ Oncology
/ Patients
/ Tumors
